Clinical CYP2D6-Mediated Pharmacokinetic Drug-Drug Interactions of DA-8010 with Paroxetine or Mirabegron in Healthy Korean Participants
Abstract
Background and Objective: DA-8010 is a selective M3 muscarinic receptor antagonist under development for overactive bladder (OAB). This study examined potential CYP2D6-mediated pharmacokinetic interactions between DA-8010 and paroxetine or mirabegron. Methods: An open-label, single-sequence, 2-part clinical study was conducted in healthy volunteers. In Part 1, the effect of paroxetine on the PK of DA-8010 was evaluated. Single-dose administration of DA-8010 5 mg was performed in both periods, with paroxetine 20 mg given once daily for 11 days in the second period. For PK characterization of DA-8010, plasma samples were obtained over a 48-hour period following dosing. Part 2 was designed to characterize reciprocal PK interactions between DA-8010 and mirabegron under multiple-dose conditions. Participants received DA-8010 at a 5 mg dose for five days during the initial phase. Subsequently, mirabegron 50 mg was administered alone for 10 days, after which coadministration with DA-8010 was continued for an additional five days. PK sampling for both DA-8010 and mirabegron was performed over 24 hours after dosing. PK parameters including maximum plasma concentration (C max ) and area under the curve (AUC) were estimated using non-compartmental analysis. CYP2D6 genotyping was performed for all participants. Results: Eighteen participants completed Part 1, while seventeen completed Part 2. Exposure to DA-8010 increased following concomitant administration with paroxetine, with…
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